The Cystic Fibrosis Core Center at Case Western Reserve University proposes to continue to pursue its goal of the conquest of cystic fibrosis. In order to achieve that goal, a multidisciplinary program ranging from studies of the molecular biology of CFTR to therapeutic trials in patients with CF is in place. Over 30 investigators from six departments receive over $6 million per year in direct support of CF- related projects. This highly interactive group of investigators depends on five cores supported by the CF Core Center: the Administrative Core, which now includes the Statistical Facility; the Epithelial Cell Culture Core which provides facilities, expertise, and cost savings for investigators using tissue culture; the Cell Physiology Core, which provides electrophysiology and videomicroscopy equipment Center investigators as well as instruction in their use; the Morphology Core, which provides access to expertise and instrumentation for electron microscopy and fluorescence light microscopy and Nomarski optic, as well as histopathology services; and the Inflammatory Mediator/BAL Core which provide samples of CF, normal, and disease control bronchoalveolar lavage fluid to investigators, as well as cost savings on assays of cytokines, eicosanoids, and intracellular signalling molecules. Besides these Cores, the Center proposes to support two feasibility projects at a time, which will allow new investigators to work on CF-related ideas, investigators established in another area to turn attention to CF, and CF investigators to try out entirely novel concepts. In the last five year period, the Center has thrived and developed active research programs in CF gene therapy, CFTR channel physiology, activation of CFTR mutants, CFTR processing, and inflammation in the CF lung. We have completed a trial of an antiinflammatory agent which reduced the rate of decline of CF lung function substantially over the four year period of the study, and is now coming into wide clinical use. Continuation of the cross-fertilization of the clinical work with the basic science will surely bring us closer to our goal of controlling CF in the next five year period, as it clearly has in the current grant period.